Formal asymmetric enone aminohydroxylation: organocatalytic one-pot synthesis of 4,5-disubstituted oxazolidinones

A formal asymmetric organocatalytic aminohydroxylation reaction of enones has been achieved via an aziridination-double S(N)2 sequence. As a part of the reaction design, the generated amino alcohol products are isolated as the corresponding oxazolidinones in good yields and excellent stereoselectivities.     

Oxidative amidation of benzyl alcohols with amino acid esters mediated by N-hydroxysuccinimide/phenyliodine diacetate

A simple protocol involving metal-free oxidative amidation of benzyl alcohols with amino acid esters has been presented. The amidation proceeds in a radical pathway unlike in conventional metal-mediated extrusion of dihydrogen. The method is advantageous in terms of metal-free conditions, nonexpensive commercial starting substrates. Also various substituents in the starting materials are tolerated and sterically hindered amino acid side chains could provide good yields of amide products.     

新手性配体(QN)2AQN的合成及其催化肉桂酸甲酯的不对称氨羟化反应研究

在AlCl₃和多聚磷酸的存在下, 以邻苯二甲酸酐和对二氟苯为原料, 通过Friedel-Crafts和环化反应, 用改进的方法以60%的产率生成1,4-二氟蒽醌. 然后通过奎宁锂与1,4-二氟蒽醌的亲核取代反应得到新型手性配体(QN)₂AQN, 产率85%. 在氧化-供氮试剂N-氯代氨基甲酸苄酯存在下, (QN)₂AQN与OsO₄原位生成的催化剂在五种肉桂酸甲酯的不对称氨羟化反应中表现出优异的对映选择性(90%～96% ee)和一般至优秀的区域选择性(75∶25～98∶2), 产率50%～70%, 高于文献报道的结果. 该手性配体易于合成, 成本低廉, 用于催化不对称氨羟化反应, 可以制备光学活性的α-氨基酸酯类化合物.     

Asymmetric synthesis of highly functionalized γ-lactams through an organocatalytic aza-Michael–Michael reaction cascade using fumaric acid amide esters as multi-reactive substrates

We developed a novel method for the asymmetric synthesis of highly functionalized γ-lactams through an organocatalytic aza-Michael–Michael reaction cascade using fumaric acid amide esters as multi-reactive substrates. Using chiral primary or secondary amine organocatalysts, we obtained two types of γ-lactams with three contiguous chiral centers in moderate to good yield with excellent enantioselectivity and diastereoselectivity.     

Facile amidation of esters with aromatic amines promoted by lanthanide tris (amide) complexes

The development of catalysts capable of catalyzing amidation of esters with amines to construct amides under mild conditions is of great importance. Compared to aliphatic amines, the direct catalytic amidation of esters with less nucleophilic aromatic amines is rather difficult. Employing simple lanthanide tris (amide) complexes Ln[N (SiMe₃)₂]₃(μ-Cl)Li (THF)₃ as the catalysts, it was found a broad range of aromatic amines and esters were efficiently converted into various amides in good yields under mild conditions. A plausible mechanism for this transformation was experimentally supported as starting from an amide exchange reaction between the lanthanide tris (amide) complex and the substrate amine.     

Access to α‐Amino Acid Esters through Palladium‐Catalyzed Oxidative Amination of Vinyl Ethers with Hydrogen Peroxide as the Oxidant and Oxygen Source

A novel and convenient palladium catalytic system for the synthesis of α‐amino acid esters from simple starting materials is reported. Hydrogen peroxide not only acts as the green oxidant, but also as the oxygen source. This strategy for the conversion of amines and vinyl ethers into highly functionalized and structurally diverse α‐amino acid esters is characterized by the simplicity of the experimental procedure, mild reaction conditions, high atom economy, scalability, and practicability.     

Two-step preparation for catalyst-free biodiesel fuel production

Biodiesel fuel was prepared by a two-step reaction: hydrolysis and methyl esterification. Hydrolysis was carried out at a subcritical state of water to obtain fatty acids from triglycerides of rapeseed oil, while the methyl esterification of the hydrolyzed products of triglycerides was treated near the supercritical methanol condition to achieve fatty acid methyl esters. Consequently, the two-step preparation was found to convert rapessed oil to fatty acid methyl esters in considerably shorter reaction time and milder reaction condition than the direct supercritical methanol treatment. The optimum reaction condition in this two-step preparation was 270°C and 20 min for hydrolysis and methyl esterification, respectively. Variables affecting the yields in hydrolysis and methyl esterification are discussed.     

Synthesis of β,β′-diamino acids from α-amino acid-derived β-lactams by ring opening with nucleophiles. Utilization in the synthesis of peptidomimetics

Ring opening of protected 3-aminoalkyl-substituted azetidin-2-ones with O-, N- or S-nucleophiles led to β,β′-diaminocarboxylic esters, amides and thioesters, respectively. The reaction outcome is improved by the addition of catalytic amounts of sodium azide. Utilization of a glycine derivative with unprotected amino function as nucleophile was possible. When bulkier amino acid esters were used, the intermediate acid azide underwent a Curtius rearrangement. The isocynates formed were trapped as the corresponding urea derivatives. Reduction of β-lactam's amide moiety led to diaminoalcohols.     

Exceptionally Simple Homologation of Protected α‐ to β‐Amino Acids in the Presence of Silica Gel

The Wolff rearrangement of α‐amino acid–derived diazoketones is simply achieved by gentle warming in a ethyl acetate/silica gel slurry containing catalytic amounts of silver trifluoroacetate. Without workup (not counting filtration and evaporation) the protected β‐amino acids are obtained in high yields (92–97%) without significant impurities. This variation avoids the laborious workup after a conventional silver‐catalyzed Wolff rearrangement. This method can be similarly applied to the synthesis of β‐amino acid methyl esters when methanol is used as solvent. No reaction occurs without silica gel.     

Solvent effect on the conformational behaviour of amino acid and oligopeptide derivatives

The solvent effect on acetyl amino acid methyl esters and C- and N-protected di- and tripeptide derivatives has been studied in deuterium oxide (D₂O), 1.1.1.3.3.3-hexafluoroisopropanol (HFiP), dimethyl sulfoxide (DMSO) and methylene chloride (CH₂Cl₂). The interpretation is based on the amide I region. For the amino acid derivatives the relative shift of the amide I signal clearly indicates the strength of the interaction with the solvent molecules. However, in HFiP and DMSO solutions the occurrence of two overlapping signals for the amide I and the ester carbonyl signal, respectively, indicates the existence of two major conformers. Knowing the solvent effects on the small amino acid esters allows the assignment of the signals in di- and tripeptide derivatives. Although the identification of turn structures in these flexible molecules is not possible, the band positions and intensity of the deconvoluted amide I region clearly shows that certain conformers can be stabilised. It can be concluded that the band profile in the amide I region is determined by the number of amino acid residues linked in the molecule, the bulkiness of the side chains and their sequence and to a major extend by the solvent properties.     

Use of Diphenyliodonium Bromide in the Synthesis of Some N-Phenyl α-Amino Acids

The N-phenyl methyl esters 4 of glycine, alanine, valine, leucine, isoleucine, phenylalanine, methionine, proline, serine, threonine, tyrosine, aspartic acid, and glutamic acid have been synthesized in good to excellent yields using diphenyliodonium bromide, AgNO₃, and a catalytic amount of CuBr starting from the relevant amino acid ester. The chiral integrity of the amino acids 5 was maintained during these reactions, which were confirmed by the synthesis of dipeptide for each N-phenyl amino acid. The structures of the new compounds were confirmed by the analysis of their IR, ¹H, and ¹³C NMR spectra in addition to CHN microanalysis or high-resolution mass spectrometry for the new N-phenyl amino acids 5 and the esters 4.     

Palladium on carbon–bromobenzene mediated esterification and transesterification

A series of carboxylic acids were converted into their corresponding esters using the Pd/C catalyzed hydrogenation conditions in the presence of catalytic bromobenzene in alcohols and the method could also be applicable for the transesterification of esters. Good to excellent yields were obtained for different aliphatic or aromatic starting materials. The success of this esterification relies on the in situ generation of hydrobromic acid (HBr) from bromobenzene which provides a mild and acidic reaction environment. The palladium catalyst exhibits a remarkable activity and is reusable for up-to three consecutive cycles.     

Radical additive cyclization in the reaction of dialkyl maleates and dialkyl fumarates with dibenzoyl peroxide

Conclusions The reaction of dialkyl esters of maleic and fumaric acids with dibenzoyl peroxide catalyzed by cupric ions in solution of the dialkyl maleates and fumarates leads to the formation of tetraalkyl esters of tetralin-1,2,3,4-tetracarboxylic acid in high yields.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 9, pp. 2151–2153, September, 1985.     

Isomerizing olefin metathesis as a strategy to access defined distributions of unsaturated compounds from Fatty acids

The dimeric palladium(I) complex [Pd(μ-Br)(t)Bu(3)P](2) was found to possess unique activity for the catalytic double-bond migration within unsaturated compounds. This isomerization catalyst is fully compatible with state-of-the-art olefin metathesis catalysts. In the presence of bifunctional catalyst systems consisting of [Pd(μ-Br)(t)Bu(3)P](2) and NHC-indylidene ruthenium complexes, unsaturated compounds are continuously converted into equilibrium mixtures of double-bond isomers, which concurrently undergo catalytic olefin metathesis. Using such highly active catalyst systems, the isomerizing olefin metathesis becomes an efficient way to access defined distributions of unsaturated compounds from olefinic substrates. Computational models were designed to predict the outcome of such reactions. The synthetic utility of isomerizing metatheses is demonstrated by various new applications. Thus, the isomerizing self-metathesis of oleic and other fatty acids and esters provides olefins along with unsaturated mono- and dicarboxylates in distributions with adjustable widths. The cross-metathesis of two olefins with different chain lengths leads to regular distributions with a mean chain length that depends on the chain length of both starting materials and their ratio. The cross-metathesis of oleic acid with ethylene serves to access olefin blends with mean chain lengths below 18 carbons, while its analogous reaction with hex-3-enedioic acid gives unsaturated dicarboxylic acids with adjustable mean chain lengths as major products. Overall, the concept of isomerizing metatheses promises to open up new synthetic opportunities for the incorporation of oleochemicals as renewable feedstocks into the chemical value chain.     

4-二甲基氨基吡啶催化合成N-保护氨基酸三氟乙酯

合成了6个未见文献报道的N-保护氨基酸三氟乙酯。4-二甲基氨基吡啶对N-保护氨基酸三氟乙酯的合成具有较高的催化活性,使三氟乙酯的合成产率大大增加。     

Catalytic diastereoselective Pauson-Khand reaction: an efficient route to enantiopure cyclopenta[c]proline derivatives

Cyclopenta[c]proline derivatives were synthesized in a stereocontrolled manner and in good yields via catalytic Pauson-Khand reactions. The starting materials, optically pure enyne amino acid derivatives, can be easily prepared by an alkenylboronic acid-mediated Mannich-type reaction. [reaction: see text]     

Direct catalytic asymmetric mannich reactions of malonates and beta-keto esters

The first catalytic asymmetric direct Mannich reaction of malonates and beta-keto esters has been developed. Malonates react with an activated N-tosyl-alpha-imino ester catalyzed by chiral tert-butyl-bisoxazoline/Cu(OTf)(2) to give the Mannich adducts in high yields and with up to 96% ee. These reactions create a chiral quaternary carbon center and it is demonstrated that this new direct Mannich reactions provides for example a new synthetic procedure for the formation of optically active beta-carboxylic ester alpha-amino acid derivatives. A series of different beta-keto esters with various ester substituents has been screened as substrates for the catalytic asymmetric direct Mannich reaction and it was found that the best results in terms of yield, diastereo- and enantioselectivity were obtained when tert-butyl esters of beta-keto esters were used as the substrate. The reaction of different beta-keto tert-butyl esters with the N-tosyl-alpha-imino ester gave the Mannich adducts in high yields, diastereo- and enantioselectivities (up to 95% ee) in the presence of chiral tert-butyl-bisoxazoline/Cu(OTf)(2) as the catalyst. To expand the synthetic utility of this direct Mannich reaction a diastereoselective decarboxylation reaction was developed for the Mannich adducts leading to a new synthetic approach to attractive optically active beta-keto alpha-amino acid derivatives. Based on the stereochemical outcome of the reactions, various approaches of the N-tosyl-alpha-imino ester to the chiral bisoxazoline/Cu(II)-substrate intermediate are discussed.     

Facile N-derivatization of alpha-amino esters and amides via benzotriazolylmethyl derivatives

Alpha-(N-substituted amino)esters were prepared in a two-step procedure from available unsubstituted alpha-amino esters. alpha-Amino esters are first converted into the corresponding N-benzotriazolylmethyl derivatives; in the second step, the benzotriazole group is substituted by various nucleophiles with or without the presence of a Lewis acid to give substituted alpha-amino esters in high overall yield under mild conditions with no signs of racemization. Boc-protected amino acids were converted into alpha-amino amides; subsequent deprotection allowed the conversion into N-substituted derivatives analogously to the alpha-amino esters, without racemization in high yields under mild conditions.     

Solution- and solid-phase synthesis of triazole oligomers that display protein-like functionality

We recently developed a new class of oligomers that contain alpha-amino acid residues linked by 1,2,3-triazole groups [Angelo, N. G.; Arora, P. S. J. Am. Chem. Soc. 2005, 127, 17134-17135]. Synthesis of these oligomers involves an iterative sequence consisting of diazotransfer and Huisgen 1,3-dipolar cycloaddition steps. In this contribution, we describe an efficient one-pot, two-step sequence for the preparation of triazoles from the corresponding amino acid-derived amines and alkynes in solution. The one-pot sequence affords the desired products in significantly higher yields than our original method. We also outline a highly effective protocol for the synthesis of these triazole-based biomimetic oligomers on the solid phase. We find that amino acid derivatives and iterative formation of triazole rings require nontraditional reaction conditions for high yields.     

Expanding the scope of the acyl-type radical addition reactions promoted by SmI2

N-acyl oxazolidinones of simple carboxylic acids and amino acids were observed to undergo successful SmI2-promoted couplings with substituted acrylamides and acrylates, affording a variety of functionalized gamma-ketoamides and -esters with yields attaining 85%. As many of these reductive couplings were previously found to be ineffective employing the corresponding 4-pyridylthio esters, the applicability of this methodology has been substantially improved. The methodology has been adapted to prepare structures related to two potent aspartate protease inhibitors, the renin inhibitor aliskiren, and the gamma-secretase inhibitor L-685,458. Finally, a convenient two-step procedure for the preparation of N-acyl oxazolidinones of N-protected amino acids, which provides consistently good yields of the corresponding imide, has been devised.